Phosphodiesterase type 4 (PDE4) is an enzyme that degrades the phosphodiester bond in the second messenger molecules of cellular cyclic adenosine monophosphate (cAMP), thereby regulating the localization, duration, and amplitude of cAMP signaling. cAMP binds to protein kinases enabling catalytic units of the protein kinases to phosphorylate substrate proteins. cAMP functions in several biochemical processes. The specific effect of cAMP depends on the protein kinase acted upon and the cell type. Sustaining cellular cAMP levels can inhibit numerous diseases and conditions. PDE4 inhibitors block the PDE4 induced degradation of cAMP thereby sustaining cellular cAMP levels and prolonging the effects of cAMP mediated physiological processes. Accordingly, PDE4 inhibitors can be valuable agents in treating or managing a number of related diseases or conditions.
Unfortunately, several PDE4 inhibiting compounds have narrow therapeutic windows and often cause undesirable side effects (i.e. nausea, diarrhea and headaches) when administered at therapeutically effective doses. Additionally, consumers continue to demand pharmaceuticals and nutraceuticals that include naturally derived active ingredients. Accordingly, the present inventors recognize a need for naturally derived PDE4 inhibitors which attain a desired level of PDE4 inhibition with little to no adverse side effects.